We seek to understand the pathogenesis of delayed cerebral arterial construction after subarachnoid hemorrhage (SAH) due to aneurysmal rupture and develop an effective treatment regimen for patients. Recent in vivo and in vitro experiments lead us to propose a specific hypothesis for an important underlying mechanism of chronic cerebral vasospasm after SAH: Complement protein extravasated into the subarachnoid clot is activated by erythrocytes denatured due to "aging" in this non- supportive environment, which stimulates inflammation and greatly accelerates hemolysis in the subarachnoid clot. We have shown that both inflammation and hemolysis provide major vasoconstrictive stimuli to cerebral arteries surrounded by subarachnoid blood. This hypothesis will be tested studying the movement of serum complement protein into subarachnoid clot and its dependence on "aging" of subarachnoid erythrocytes using non-specific tracers, radiolabelled complement protein, and immunohistochemistry. A correlation between inflammation and generation of activated chemotactic complement will be sought. The rate of hemolysis in subarachnoid blood clot will be determined as a function of time, an a specific dependence on complement- induced hemolysis determined by immunohistochemical identification of "membrane attack complex." The prophylactic value of immunosuppression by partial specific decomplementation will be determined in our animal model of cerebral vasospasm, angiographically as well as more specifically against hemolysis and subarachnoid inflammation. By inhibiting rapid hemolysis and activation of complement, a whole cycle of threatening events may be averted. In vitro studies will focus on identification of the vasoactive factors in erythrocyte lysate and their possible role in activation of the protein kinase C system.